Meniscus allograft transplantation has become a viable treatment option for selected symptomatic patients who have undergone a complete or near-complete meniscectomy. Preliminary basic and clinical studies have suggested that meniscus allograft transplantation may help alleviate pain and improve knee function. However, the efficacy of transplantation to restore normal meniscus function compromised by meniscectomy has not been rigorously evaluated. There has been a scarcity of converging evidence from both clinical and basic science studies. Critically lacking are quantitative in vivo data and mechanistic descriptions of how meniscus allograft transplantation affects the knee joint function and mechanics. Such data and knowledge bases not only provide direct, most relevant scientific evidence for optimizing the clinical care, but also are much needed for guiding the development of tissue-engineered meniscus constructs. The proposed research is the first attempt to develop such a knowledge base by studying the effects of meniscus allograft transplantation on tibiofemoral kinematics and contact congruency in vivo and in silico. Our long-term goal is to establish a biomechanical science base and a computerized clinical utility for designing individual-optimized meniscus allograft transplantation. Our specific aims are (1) to characterize the in vivo changes in tibiofemoral kinematics and contact congruency in patients before and after treatment with meniscal transplant surgery during daily activities (level walking, squatting), and (2) to develop and validate a computational in silico model that describes mechanistically the effects of meniscus transplantation of varied characteristics on joint kinematics and contact congruency. We will measure 10 patients' tibiofemoral kinematics using a dynamic biplane radiography system, muscle activations using a wireless EMG system, and whole-body kinematics- kinetics using an optical motion capture system along with an instrumented treadmill. We will obtain high- resolution computed tomography (CT) and magnetic resonance imaging (MRI) scans of the patients. With the data, we will develop patient-specific models using an approach combining forward dynamic simulation and finite element modeling. We will validate the model based on both within-patient and cross-patient predictions. Successful fulfillment of these research aims will build a new biomechanical science foundation and a validated modeling framework for our future pursuit of individual-optimized meniscus transplantation that not only restores joint congruency but also promotes long-term joint health. PUBLIC HEALTH RELEVANCE: Meniscectomy is the most common orthopaedic surgical procedure performed in the United States and has deleterious consequences such as osteoarthritis and muscle dysfunction. Although meniscus transplant surgery has become a viable treatment option to restore normal meniscus function compromised by meniscectomy, its efficacy has not been rigorously evaluated. This grant application seeks to study the effects of meniscus allograft transplantation on tibiofemoral kinematics and contact mechanics using computer models developed from in vivo data.